Glucocorticoid receptors and growth inhibitory effects of dexamethasone in human lung cancer cell lines

Glucocorticoid receptors and growth inhibitory effects of dexamethasone in human lung cancer cell lines
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DOI:
10.1016/0959-8049(95)00431-9
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发表时间:
1995-11-01
影响因子:
8.4
通讯作者:
Havemann, K
Havemann, K
中科院分区:
医学1区
文献类型:
--
作者:
Hofmann, J;Kaiser, U;Havemann, K

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研究了6个小细胞肺癌(SCLC)和13个非小细胞肺癌(NSCLC;4个腺癌、4个鳞癌、4个大细胞癌和1个间皮瘤)细胞系糖皮质激素受体(GR)的表达及地塞米松和抗糖皮质激素RU-486对细胞生长的影响。通过全细胞分析和胞浆受体分析,所有细胞系都含有合成的糖皮质激素地塞米松的特异和可饱和的结合位点。免疫细胞化学证实癌细胞中存在GRs。在非小细胞肺癌细胞系中,GRs大量存在(37-638fmol/mg胞浆蛋白)。在小细胞肺癌细胞系中,也可检测到GRs,但浓度相当低。地塞米松对两种鳞癌细胞系(EPLC-32M1和NCI-H157)、一种腺癌细胞系(A-549)、一种大细胞癌细胞系(LCLC-97TM1)和一种间皮瘤细胞系(MSTO-211H)的生长有抑制作用。所有对地塞米松敏感的细胞系都有较高的GR浓度(大于或等于164fmol/mg胞浆蛋白)。抗糖皮质激素RU-486单独给药时几乎没有活性,但能够阻断地塞米松的生长抑制作用。结果表明,糖皮质激素可能抑制个体非小细胞肺癌的进展。
Expression of glucocorticoid receptors (GR) and growth effects of dexamethasone and the antiglucocorticoid RU-486 were investigated in six cell lines originating from small cell lung cancer (SCLC) and 13 cell lines from non-small cell lung cancer (NSCLC; four adenocarcinoma, four squamous cell carcinoma, four large cell carcinoma and one mesothelioma). All cell lines contained specific and saturable binding sites for the synthetic glucocorticoid dexamethasone, as determined by whole cell assays and by cytosolic receptor assays. The presence of GRs in the carcinoma cells was confirmed by imnunocytochemistry. In NSCLC cell lines, GRs were present in large amounts (37-638 fmol/mg cytosolic protein). in SCLC cell lines, GRs were also detectable but in considerably lower concentrations. Growth inhibitory effects of dexamethasone were seen in the cultures of two squamous cell carcinoma lines (EPLC-32M1 and NCI-H157), one adenocarcinoma line (A-549), one large cell carcinoma cell line (LCLC-97TM1) and the cell line of a mesothelioma (MSTO-211H). All cell lines responsive to dexamethasone had high GR concentrations (greater than or equal to 164 fmol/mg cytosolic protein). The antiglucocorticoid RU-486 was virtually inactive when administered alone but was able to block the growth-inhibitory effect of dexamethasone. The results indicate that glucocorticoids may inhibit the progression of individual non-small cell lung carcinoma.